Project Summary/Abstract In the vestibular system, accelerations of the head are transduced and processed prior to transmission to the brain. Prior research has shown that responses of primary afferent neurons from the semicircular canal deviate from canal biomechanics, and has implicated signal processing by the hair cell?primary afferent synapse in shaping the response. Afferent processing is complex due to both the convergence of multiple hair cells onto a single afferent, and three modes of synaptic transmission between hair cell and afferent. Type I hair cells are enveloped by their afferent in a calyceal ending that forms a restricted volume, or cleft, where rapid excitatory synaptic transmission, via glutamatergic AMPA receptors, is modulated both pre- and post-synaptically by K+, H+, and Ca2+ accumulation. By contrast, type II hair cells make synaptic contact either onto conventional bouton endings, or onto the external face of calyces that envelop type I hair cells. The afferent taxonomy is equally complex, and includes three major classes of hair cell to afferent convergence. The simplest are the pure bouton afferents, where hair cells converge onto their afferent via bouton endings. Increased complexity is found at calyceal endings, composed of either a simple calyx in which the afferent envelops a single hair cell, or complex calyces, where the afferent encompasses two or more. The most complex afferents are the dimorphic endings that contact both type I and type II hair cells via a combination of bouton and inner? and outer?face calyceal synapses. Attempts to correlate and rationalize afferent physiology with morphology have been impeded by two outstanding problems. The first is that morphophysiological studies allow a correlation between the number of bouton and calyceal endings and afferent physiology, but cannot estimate the number of type II hair cells that synapse onto the external face of a calyx. As a consequence, the external face synapses have remained cryptic in prior studies, and the impact of these contacts on afferent physiology remain obscure. The second problem is that little is known about the calculus of synaptic transmission at any ending, or how the geometry of quantal and non-quantal transmission determines the dynamics of afferent discharge. To surmount these problems and to more fully understand the variations in synaptic transmission, we will capitalize on our recently developed simultaneous recording from hair cells and their associated afferents to characterize synaptic transmission between type I and type II hair cells in dimorphic endings. Specifically, we will characterize the rapid glutamate?mediated transmission and its modulation by ion accumulation in the cleft between the type I hair cell and the inner face of the afferent calyx. We will contrast this mode of transmission to that between the calyx and type II hair cells that synapse onto the outer face of the calyx. Finally, we will characterize the type II hair cell synaptic input onto boutons, as well as the electrical properties of the dendritic arbor connecting type II hair cell boutons with the parent fiber in dimorphic afferents.